biostudies-arrayexpressMarie RumplerMus musculushttps://www.ebi.ac.uk/biostudies/studies/E-MTAB-14195NAD+ is a crucial cofactor for the activity of various enzymes, including sirtuins and ADP-ribosyl transferases, and its decline is associated with aging and metabolic-related diseases. Therefore, a strong interest has been raised in the therapeutic use of NAD+ precursors (Vitamin B3s), but many suffer from poor bioavailability and adverse effects. This study characterizes the metabolic impact of dihydronicotinamide riboside, a recently identified novel form of NAD+ precursor. Upon oral administration in mice, NRH reaches all tissues examined. Chronic administration in low-fat diet-fed mice showed negligible metabolic effects, while high-fat diet-fed mice were protected against body weight gain and glucose intolerance. However, our study also unveiled potential side effects at higher doses. Thus, NRH could constitute an alternative NAD+ boosting strategy to prevent diet-induced metabolic complications and conditions associated with low NAD+ levels, but the therapeutic window must be optimized to maximize benefits and minimize risks. Mice were either low-fat diet fed or high-fat diet-fet, and either in control group or supplemented with NRH groups (NRH100 and NRH400) for up to 16 weeks. Tissues were collected to extract RNA and perform RNA-seq (BRB-seq protocol)biostudies-arrayexpressSequencing - Libraries were pooled per mouse organ and sequenced on a NovaseqNucleic Acid Extraction - Total mRNAs were extracted as described previously (Ratajczak, J. et al. Nat Commun, 2016)Library Construction - BRB-seq libraries were generated using a MERCURIUS BRB-seq kit (Alithea Genomics, #10813) according to the manufacturers’ instructionsSample Collection - Male and Female C57Bl/6NTac were purchased from Taconic. All mice were kept in a standard temperature- and humidity-controlled environment with a 12h:12h light-dark cycle. Mice had nesting material and ad libitum access to water and commercial diets. For the studies in Figures 1-3, mice were fed a regular mouse housing diet (Safe®150). For the high-fat diet study, we used D12492 from Research Diets, while using D12450J as a sucrose matched control. NRH was provided to mice in the drinking water, at a concentration of 0.1% of 0.4%, which approximately leads to a dose of 100 mg/kg*day or 400 mg/kg*day assuming mice drink around 3 ml per day and weight around 30 grams. Water bottles were renewed twice a week with a fresh solution. For the high-fat diet, the dose of NRH in the water bottles was adjusted weekly according to the average body weight of the cage. All animal experiments were carried out according to national Swiss and EU ethical guidelines and approved by the local animal experimentation committee under licenses VD2770.1, VD3647 and VD3841.OrganizationMINSEQE ScoreAssays and DataProcessed DataMAGE-TAB FilesData Transformation - The raw read count matrix was generated using FastReadCounter (Version 1.1)(https://github.com/DeplanckeLab/FastReadCounter) ran on the tagged bam file generated by STARsolo. The data was also demultiplexed for ArrayExpress submission using BRBseqTools (Version 1.6.1)(https://github.com/DeplanckeLab/BRB-seqTools).Sequence Alignment - RNA-seq reads were aligned to the reference mouse mm10 genome (GRCm38, Ensembl release 102) using STARsolo (Version 2.7.10a) (Dobin, Bioinformatics, 2013). Reads mapping to multiple positions were excluded. STARsolo also generated the UMI count matrix.MetabolomicsUnknownTranscriptomicsGenomicsProteomicsIllumina NovaSeq 6000RNA-seq of coding RNAMus musculusMarie RumplerJulie RusseilSofia MocoCarles CantoBart DeplanckeFaisal HayatStefan ChristenVincent GardeuxHoria HashimiClémence SteinerJudith Giroud-GerbetantMaria Pilar GinerRiekelt HoutkooperKasper VintenMagali JoffraudJose Luis Sanchez GarciaMarie MigaudGuido Van MierloLaurine Van GijnfalseMetabolic effects of chronic dihydronicotinamide riboside (NRH) administration in mice - RNA-seq of murine tissues (NRH treatment)NAD+ is a crucial cofactor for the activity of various enzymes, including sirtuins and ADP-ribosyl transferases, and its decline is associated with aging and metabolic-related diseases. Therefore, a strong interest has been raised in the therapeutic use of NAD+ precursors (Vitamin B3s), but many suffer from poor bioavailability and adverse effects. This study characterizes the metabolic impact of dihydronicotinamide riboside, a recently identified novel form of NAD+ precursor. Upon oral administration in mice, NRH reaches all tissues examined. Chronic administration in low-fat diet-fed mice showed negligible metabolic effects, while high-fat diet-fed mice were protected against body weight gain and glucose intolerance. However, our study also unveiled potential side effects at higher doses. Thus, NRH could constitute an alternative NAD+ boosting strategy to prevent diet-induced metabolic complications and conditions associated with low NAD+ levels, but the therapeutic window must be optimized to maximize benefits and minimize risks. Mice were either low-fat diet fed or high-fat diet-fet, and either in control group or supplemented with NRH groups (NRH100 and NRH400) for up to 16 weeks. Tissues were collected to extract RNA and perform RNA-seq (BRB-seq protocol)2026-03-09T00:00:00Z2026-03-09T02:02:54.061Z2024-06-20T19:26:01.088ZE-MTAB-14195ERP161346E-MTAB-14177EFO_0002944EFO_0004170EFO_0004917EFO_0005518EFO_0003816EFO_0003738EFO_0004184